STRUCTURAL BIOLOGY OF MEMBRANE PROTEINS SBIR/STTR ANNOUNCEMENT

PA NUMBER:  PA-02-108 

RELEASE DATE:  May 16, 2002

APPLICATION RECEIPT DATES: April 1, August 1, December 1

EXPIRATION DATE:  April 10, 2005 unless reissued

PARTICIPATING INSTITUTES AND CENTERS (ICs): 

National Institute of General Medical Sciences (NIGMS)
 (http://www.nigms.nih.gov/)
National Cancer Institute (NCI)
 (http://www.nci.nih.gov/)
National Heart, Lung, and Blood Institute (NHLBI)
 (http://www.nhlbi.nih.gov/)
National Institute on Aging (NIA)
 (http://www.nia.nih.gov/)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
 (http://www.niams.nih.gov/)
National Institute on Deafness and Communication Disorders (NIDCD)
 (http://www.nidcd.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
 (http://www.niddk.nih.gov/)
National Institute on Drug Abuse (NIDA)
 (http://www.nida.nih.gov/)
National Institute of Environmental Health Sciences (NIEHS)
 (http://www.niehs.nih.gov/)
National Institute of Mental Health (NIMH)
 (http://www.nimh.nih.gov/)
National Institute of Neurological Disorders and Stroke (NINDS)
 (http://www.ninds.nih.gov/)
National Center for Research Resources (NCRR)
 (http://www.ncrr.nih.gov/)

THIS PA CONTAINS THE FOLLOWING INFORMATION

o Purpose of this PA
o Research Objectives
o Mechanism(s) of Support 
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Submitting an Application
o Peer Review Process
o Review Criteria
o Award Criteria
o Required Federal Citations

PURPOSE OF THIS PA

The purpose of this PA is to encourage researchers to solve the structures of 
membrane proteins at atomic resolution and to develop the tools needed to solve 
these structures.  Considerable research on the structure and function of 
membrane proteins is under way.  Yet, relatively few investigators use x-ray 
crystallography, electron diffraction, or nuclear magnetic resonance (NMR) 
spectroscopy to study the structures of these proteins directly.  During the 
past decade, investigators have determined the structures of approximately 30 
membrane proteins.  The solution of each structure has been a major contribution 
to a particular area of science (see 
http://blanco.biomol.uci.edu/Membrane_Proteins_xtal.html).  This progress 
clearly demonstrates that determining the structures of membrane proteins is 
feasible.  However, the rate of solving soluble protein structures also has 
accelerated greatly during the past decade.  Thus, a gap remains between 
understanding membrane proteins and understanding their soluble protein 
counterparts.  

The National Institutes of Health (NIH) has undertaken the Protein Structure 
Initiative (PSI) to accelerate further the rate of solving protein structures. 
(See:  http://www.nigms.nih.gov/funding/psi.html).  Some PSI centers include 
efforts to determine the structures of membrane proteins, and the PAs for the 
PSI encourage the development of technologies for high-throughput approaches to 
determine the structures of these proteins (see  
http://grants.nih.gov/grants/guide/pa-files/PA-99-116.html).  Nonetheless, a 
separate program initiative is needed to focus primarily on membrane proteins 
and the development of methods for solving their structures.  An increase in the 
number of known membrane protein structures will help to enhance understanding 
of many basic phenomena underlying the cellular functions essential to human 
health and may lead directly to products that have commercial value and societal 
impact.

This PA is offered through the NIH Small Business Innovation Research (SBIR) and 
Small Business Technology Transfer (STTR) grant program and is directed to 
eligible small businesses.  A parallel PA, Structural Biology of Membrane 
Proteins (PA-02-060), offers support for applicants other than small businesses 
to conduct investigator-initiated (R01) research of identical technical and 
scientific scope (see http://grants.nih.gov/grants/guide/pa-files/PA-02-060.html 
and addendum http://grants.nih.gov/grants/guide/notice-files/NOT-DA-02-004.html).

RESEARCH OBJECTIVES 

Membrane proteins have a crucial role in many cellular and physiological 
processes.  They are essential mediators of the transfer of material and 
information between cells and their environment, between compartments within 
cells, and between compartments of organ systems.  Membrane proteins that 
function normally are vital to health, and specific defects are associated with 
many known disease states.  Membrane proteins are the targets of many 
pharmacologically and toxicologically active substances and are responsible, in 
part, for the uptake, metabolism, and clearance of these substances.  

Membrane proteins are thus commercially important.  Knowledge of the structure 
of a particular membrane protein may be commercially valuable in itself or may 
lead to the development of commercially valuable agonists, antagonists, or 
inhibitors.  Research tools that can help researchers in academic laboratories 
solve the structure of membrane proteins occupy a niche market, but may be 
commercially viable and would have significant societal impact by contributing 
to the overall NIH effort to stimulate research on the structure of membrane 
proteins.

Despite the importance of membrane proteins, knowledge of their high resolution 
structures and mechanisms of action has lagged far behind the knowledge of these 
properties of proteins in general.  This gap in understanding has resulted from 
the difficulties of obtaining x-ray-diffraction-quality crystals for membrane 
proteins and of applying well-developed solution NMR methods to the study of 
most membrane proteins.  Because of these difficulties, many investigators have 
been reluctant to pursue high-resolution studies of the structures of membrane 
proteins.  

Recently, however, advances in crystallization and analysis of proteins by x-ray 
and electron diffraction and improvements in NMR methods offer new 
opportunities.  Further, the solution of crystal structures, after suitable 
crystals are obtained, has, in many cases, become sufficiently routine that 
crystallization itself is often the more major undertaking.  For this PA, 
therefore, protein production, protein crystallization, and the solution of 
protein structures are all worthy aims.

The specific objectives of this PA are to encourage small businesses to:

1) Undertake the challenge of solving the structures of membrane proteins, and

2) Further develop methods and reagents for studying the structures of membrane 
proteins at atomic resolution.

Examples of methods that need specific attention include, but are not limited, 
to methods for:

o  Overexpression of native and modified membrane proteins

o  Isolation, purification, and stabilization of membrane proteins, including 
development of new detergents and non-detergent solubilization agents

o  Crystallization of membrane proteins and crystal manipulation that could 
facilitate data collection

o  Electron diffraction, particularly for the production of suitable two-
dimensional crystals

o  NMR analysis of membrane proteins in solution, micelles, and their native 
lipid environments

o  Elucidating the organization of lipid and detergent molecules within protein 
crystalline arrays (e.g., neutron diffraction).

This PA emphasizes x-ray or electron diffraction and NMR spectroscopy because 
these techniques currently show the most promise for producing the most complete 
high-resolution information for the largest number of proteins.  However, we are 
also interested in other methods that can provide atomic-resolution information 
in selected cases.

Much of the research in this area is likely to be collaborative efforts between 
biochemists and molecular biologists, with expertise in the isolation and 
characterization of membrane-bound proteins, and biophysicists, with expertise 
in x-ray crystallography, NMR, and other structural methods.  A major aim of 
this PA is to stimulate these collaborations.

Listed below are examples of the types of membrane protein systems that are of 
particular interest to the participating institutes:

NIGMS:  Energy transducing membranes of mitochondria, chloroplasts, and 
bacterial cell membranes involved in electron transport and ATP synthesis; 
channels, pores, and transporters of ions, substrates, and macromolecules 
between intracellular compartments and between the cell and its environment; 
enzymes in the synthesis and metabolism of lipids, membrane-associated and 
secreted proteins, and glycoconjugates; cytoskeletal proteins, including those 
required for intracellular vesicle transport, cell motility, and cell division; 
regulators of cell-cell communication, differentiation, and growth; receptors 
relevant to cell-cycle regulation, mechanisms of anesthetic action, and trauma 
and burn physiology; transporters and enzymes responsible for the uptake, 
metabolism, and clearance of drugs or other effects on the bioavailability, 
pharmacokinetics, or action of drugs; targets of drug action and toxicity, 
including targets of naturally occurring toxins and venoms; and enzymes involved 
in the biosynthesis of natural products.

NCI:  Membrane proteins and membrane complexes associated with the biology, 
diagnosis and treatment of cancer.  These include membrane proteins whose 
alterations have been linked to the development and progression of cancer or 
that are part of cancer-related signaling pathways; proteins associated with the 
extracellular matrix (for example, laminins and fibronectin); and proteins with 
potential as diagnostic markers and/or therapeutic targets.  NCI is also 
soliciting applications focused on the development of new approaches and 
technologies for the isolation, purification, and structure determination of 
these proteins.  Applicants strictly focused on technology may wish to consider 
applying under the NCI Innovative Molecular Applications of Technology Program 
(see http://otir.nci.nih.gov/tech/funding.html).

NIAMS:  Membrane protein systems with specific relevance to muscle function and 
disease; bone and cartilage function and disease; and skin function and disease.  
Examples include: membrane proteins involved in excitation, relaxation, force 
transduction, cellular homeostasis, and metabolism; regulators of cell-cell 
communication and attachment (e.g., costameres, myotendinous and neuromuscular 
junctions); ion channels, receptors, transporters, and enzymes that affect the 
function and hypertrophy or atrophy of muscles; membrane proteins of skin 
involved in establishment of the stratum corneum barrier, epidermal cell-cell 
attachment and communication, transmembrane signaling and transport, and cell 
movement, including genetic and acquired diseases of the skin in which the 
membrane protein is defective or targeted (which may encompass both benign and 
malignant hyperproliferative diseases).

NIDA:  Receptors and transporters relevant to drug abuse research.  These 
proteins include: the cannabinoid CB1 and CB2 receptors; the vanilloid receptor; 
the orphanin receptor; the mu, delta, and kappa opioid receptors; the neuronal 
nicotinic receptor subtypes; the NMDA receptor complex; the metabotropic 
glutamate receptors I-III; the GABA-A receptor; the dopamine, serotonin, and 
norepinephrine transporters; and any other neuropeptide receptors that are 
affected by drugs of abuse.

NIDCD:  Membrane proteins involved in the auditory, vestibular, olfactory, 
taste, voice, speech and language sensory systems.  Eukaryotic proteins of 
interest include: transporters, ion channels, ligand receptors, G-protein 
coupled receptors, transcription and associated factors, motor and motor 
associated proteins, growth factor receptors, and cytoskeletal structural 
components involved in the function of these sensory and neural functions.  
Prokaryotic membrane proteins of interest include: proteins from numerous viral 
and microbial organisms involved in otitis media or serving as identifiable 
markers (such as muscin)for middle ear infections.

NIDDK:  Membrane protein systems with specific relevance to diseases of 
transport, such as cystic fibrosis and peroxisomal biogenesis disorders; 
carbohydrate metabolism and its hormonal control; diabetes mellitus; hormone 
receptors and signal transduction; endocrine disorders; normal and abnormal 
processes of lipid, protein, amino acid, urea, pyrimidine, metal ion, and 
steroid metabolism; and genetic metabolic disorders.  Proteins should be of 
mammalian origin.  Studies of proteins of prokaryotic or lower eukaryotic origin 
should be proposed as models for mammalian systems.  An example is the ATP 
Binding Cassette transporter superfamily or traffic ATPases in bacteria and 
yeast, which serve as models for the cystic fibrosis transmembrane regulator 
(CFTR).

NIEHS:  Membrane proteins and enzymes involved in the response of cells to 
environmental toxicants.  These proteins and enzymes may include the components 
of the stress signaling pathway or ion channels involved in the transport of 
xenobiotics (e.g., membrane transporters such as PgP, MDR, and MRP2); 
transporters and enzymes responsible for the uptake and clearance of 
environmental toxicants; targets of toxicant action, including the Ah receptor 
and non-classical receptors for endocrine-disrupting agents; and membrane-bound 
heat shock proteins.

NIA, NIMH, and NINDS:  Neurotransmitter and growth factor receptors, 
transporters, ion pumps, voltage- and ligand-gated ion channels (e.g., those 
involved in channelopathy), trafficking proteins, mitochondrial proteins, 
structural proteins and other proteins involved in the normal function and 
pathology of cells (neurons and glia) in the central and peripheral nervous 
systems.  Also, proteins involved in synaptic transmission and in the 
regulation, metabolism, homeostasis, and signaling in the brain during functions 
such as learning, memory, or cognition, during development and aging into late-
life, and in disorders of the central nervous system.  

NCRR:  The Biomedical Technology Division is interested the development of new 
technologies such as instrumentation and methodologies that will enhance the 
capacity to elucidate structures of membrane proteins.

SUMMARY

The purpose of this program announcement is to stimulate research leading to the 
solution of membrane protein structures at atomic resolution.  The above lists 
of membrane proteins are not meant to be exclusive.  Structural information 
obtained for any membrane protein will contribute to the understanding of 
general principles that underlie the structure and function of all membrane 
proteins.  The participating institutes also support research on non-membrane 
proteins associated with many of the cellular functions listed above.  However, 
this PA emphasizes the need for additional research on structural aspects of 
membrane proteins involved in these processes and the need to develop new tools 
to study membrane protein structures.

MECHANISM OF SUPPORT

This PA will use the SBIR (R43, R44) and STTR (R41, R42) award mechanisms, which 
are designed to encourage development of technology by eligible small 
businesses.  As an applicant, you will be solely responsible for planning, 
directing, and executing the proposed project.  You should read this PA in 
conjunction with the "Omnibus Solicitation of the National Institutes of Health 
for Small Business Innovation Research (SBIR) and Small Business Technology 
Transfer (STTR) Grant Applications", which describes the SBIR/STTR grant program 
(see http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf).
 
ELIGIBLE INSTITUTIONS

You may submit (an) application(s) if your institution is an eligible, domestic, 
for-profit small business organization, as described for SBIR and STTR grant 
applications in the Omnibus Solicitation.  We encourage you to access this 
solicitation for information on eligibility requirements (see 
http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf).

Eligibility for the parallel PA (Structural Biology of Membrane Proteins, PA-02-
060) is broader and encompasses foreign and domestic, for-profit and non-profit, 
and public and private organizations, such as universities, colleges, hospitals, 
laboratories, companies, units of State and local governments, and eligible 
agencies of the Federal government.  (See http://grants.nih.gov/grants/guide/pa-
files/PA-02-060.html and addendum: http://grants.nih.gov/grants/guide/notice-
files/NOT-DA-02-004.html).  

INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS

Any individuals with the skills, knowledge, and resources necessary to carry out 
the proposed research are invited to work with their institution to develop an 
application for support.  Individuals from underrepresented racial and ethnic 
groups as well as individuals with disabilities are always encouraged to apply 
for NIH programs.

SPECIAL REQUIREMENTS

You are reminded that NIH policy requires the timely publication of structural 
study results and the deposition of atomic coordinates of solved protein 
structures into structural databases immediately upon publication of results 
(see http://grants.nih.gov/grants/guide/notice-files/not99-010.html).

WHERE TO SEND INQUIRIES

We encourage your inquiries concerning this PA and welcome the opportunity to 
answer questions from potential applicants.  Inquiries may fall into three 
areas: scientific/research, peer review, and financial or grants management 
issues:

o Direct your questions about scientific/research issues to:

Peter C. Preusch, Ph.D.
Division of Pharmacology, Physiology, and Biological Chemistry
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-5938
FAX:  (301) 480-2802
Email:  preuschp@nigms.nih.gov

Jean Chin, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-2485
FAX:  (301) 480-2004
Email:  chinj@nigms.nih.gov

John C. Norvell, Ph.D.
Division of Cell Biology and Biophysics
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-0533
FAX:  (301) 480-2004
Email:  norvellj@nigms.nih.gov

Daniel Gallahan, Ph.D.
Chief, Structural Biology and Molecular Applications Branch
Program Director, Cancer Cell Biology Branch
Division of Cancer Biology
National Cancer Institute
Room 5000, EPN
6130 Executive Blvd.
Rockville, MD  20892-7385
Telephone:  (301) 435-5226
FAX:  (301) 480-2854
Email:  dg13w@nih.gov

Susan E. Old, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 9150 (MSC 7940)
Bethesda, MD 20892-7940
Telephone:  (301) 435-0477
FAX:  (301) 480-1336
Email: so40y@nih.gov

Bradley C. Wise, Ph.D.
Program Director, Fundamental Neuroscience
Neuroscience and Neuropsychology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 3C307, MSC 9205
Bethesda, MD   20892-9205
Telephone: (301) 496-9350
FAX: (301) 496-1494
Email:  wiseb@nia.nih.gov

Richard W. Lymn, Ph.D.
Muscle Biology Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-5128
FAX:  (301) 480-4543
Email:  lymnr@mail.nih.gov

Rao Rapaka, Ph.D.
Paul Hillery, Ph.D.
Division of Neuroscience and Behavioral Research
National Institute on Drug Abuse
6001 Executive Boulevard, Room 4282, MSC 9555
Bethesda, MD  20892-9555
Telephone: (301)-443-6275
Fax: (301) 594-6043
Email:  ph44x@nih.gov

Nancy L. Freeman, Ph.D.
National Institute on Deafness and Other Communication Disorders
Executive Plaza South-400C
6120 Executive Blvd, MSC 7180
Bethesda, MD 20892-7180
Telephone:  (301) 402-3458
FAX: (301) 402-6251
Email:  nancy_freeman@NIH.gov

Salvatore Sechi, Ph.D.
Director, Proteomic Program
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd. Rm 611
Bethesda, MD 20892-5460
Telephone:  (301) 594-8814
FAX: (301) 480-2688
Email:  Salvatore_Sechi@nih.gov

Claudia Thompson, Ph.D.
Chemical Exposures and Molecular Biology Branch
National Institute of Environmental Health Sciences
P.O. Box 12233, MD EC-21
Research Triangle Park, NC  27709
Telephone:  (919) 541-4638
FAX:  (919) 316-4606
Email:  thompso1@niehs.nih.gov
 
Margaret C. Grabb, Ph.D.
Chief, SBIR and STTR Programs 
Translational Research and Scientific Technology Office
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health, NIH
6001 Executive Blvd., Rm 7201 MSC 9645
Bethesda, MD 20892-9645
Tel:  (301) 443-3563
Fax: (301) 443-1731
Email:  mgrabb@mail.nih.gov

Randall R. Stewart, Ph.D.
Program Director for Channels, Synapses and Circuits
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Neuroscience Center, Room 2135
6001 Executive Blvd.
Bethesda, MD 20892-9523
Telephone:  (301) 496-1917
FAX:  (301) 402-1501
Email:  stewartr@ninds.nih.gov

Amy L. Swain, Ph.D. 
Biomedical Technology Division, NCRR 
6705 Rockledge Drive 
Room 6154, MSC 7965 
Bethesda, MD 20892-7965 
Telephone:  (301) 435-0752 
FAX:  (301) 480-3659 
Email:  swaina@ncrr.nih.gov

o Direct your questions about peer review issues to:

Stephen M. Nigida, Jr., Ph.D.
Center for Scientific Review
Room 4212; MSC 7812
6701 Rockledge Drive
Bethesda, Maryland  20817
Telephone: (301) 435-1222
Fax: (301) 480-4042
Email: nigidas@csr.nih.gov

o Direct your questions about financial or grants management matters to:

Ms. Grace Tuanmu
Grants Administration Branch
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-5520
FAX:  (301) 480-2554
Email:  tuanmug@nigms.nih.gov

Mr. William Wells
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Suite 243
Bethesda, MD 20892
Telephone:  (301) 496-8796
Fax:  (301) 496-8601
Email:  ww14j@nih.gov

Ms. Shelia Ortiz
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7174, MSC 7926
Bethesda, MD 20892-7926
Telephone: (301) 435-0166
FAX: (301) 480-3310
Email: ortizs@nhlbi.nih.gov

Ms. Linda Whipp
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Email:  WhippL@nia.nih.gov

Mr. Michael Morse
Grants Management Branch
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, MSC 6500
Bethesda, MD  20892-6500
Telephone:  (301) 594-3535
FAX:  (301) 480-5450
Email:  morsem@mail.nih.gov

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9541
Bethesda, MD  20892-9541
Telephone:  (301)-443-6710
Email:  gf6s@nih.gov

Ms. Sara C. Stone
Chief, Grants Management Branch
National Institute of Deafness and Communication Disorders
Executive Plaza South, Room 400B
6120 Executive Boulevard, MSC-7180
Bethesda, MD 20892-7180
Telephone:  (301) 402-0909
FAX:  (301) 402-1758
Email:  stones@nidcd.nih.gov 

Ms. Kathleen Shino
Division of Extramural Activities
National Institute of Diabetes and Digestive and Kidney Diseases
2 Democracy Plaza Room 708
Bethesda, MD 20892
Telephone:  (301) 594-8869
FAX:  (301) 480-3504
Email:  shinok@extra.niddk.nih.gov

Mr. Dwight Dolby
Grants Management Branch
National Institute of Environmental Health Sciences
P.O. Box 12233, MD EC-22
Research Triangle Park, NC  27709
Telephone:  (919) 541-2749
FAX:  (919) 541-2860
Email:  dolby@niehs.nih.gov

Ms. Kathy R. Hancock (For NIMH)
Grants Management Specialist
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17
Bethesda, MD  20892
Phone:  (301) 496-5482
Fax:  (301) 480-4782
Email:  hancockk@mail.nih.gov

Ms. Chris Zimmerman
Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Blvd, Room 3290, NSC 3264
Bethesda, MD 20892-9537
Telephone:  (301) 496-9231
FAX:  (301) 402-0219
Email:  cz3z@nih.gov

Mr. Paul Karadbil
Office of Grants Management
National Center for Research Resources
6705 Rockledge Drive, Room 6086
Bethesda, Maryland 20892-7965
Telephone:  (301) 435-0844
FAX:  (301) 480-3777
Email: paulk@ncrr.nih.gov

SUBMITTING AN APPLICATION

You may submit your application as a Phase I or Phase II application or as a 
Fast Track pair of Phase I and Phase II applications.  See "Specific 
Instructions" below. 

Applications must be prepared using the SBIR and STTR application instructions 
and forms.  These are available at http://grants.nih.gov/grants/funding/sbir.htm 
in an interactive PDF format.  The PDF files are hyperlinked as Appendices A 
through E subtopics under the SBIR/STTR Phase I Solicitation link.

APPLICATION RECEIPT DATES:  Applications submitted in response to this PA will 
be accepted at the following application deadlines: April 1, August 1, and 
December 1.

SPECIFIC INSTRUCTIONS FOR PHASE I APPLICATIONS:  Application forms, 
requirements, and procedures are the same as listed in the Omnibus Solicitation 
for Phase I SBIR/STTR Grant applications 
(http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf), except for the 
following:

o  Type the title and number of this PA on line 2 on the face page of the 
application.

o  The Omnibus Solicitation states levels for Phase I and Phase II budgets that 
are guidelines, not ceilings.  For this PA, we will consider larger budgets for 
longer periods of time, if they are well justified and necessary to complete the 
proposed research and development.  Applications for $100,000 may be submitted 
in modular form.  Applications for over $100,000 must include a detailed budget 
and budget justification.

SPECIFIC INSTRUCTIONS FOR Phase II Applications:  We will only accept Phase II 
applications as competing continuations of previously funded NIH Phase I SBIR or 
STTR awards.  The Phase II application must be for developmental work that is a 
logical extension of the feasibility research conducted during Phase I.  When 
preparing an application for a Phase II award, you should follow the 
instructions for NIH Phase II SBIR or STTR applications.  The instructions and 
forms for a Phase II SBIR and STTR award are available at 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

SPECIFIC INSTRUCTIONS FOR Fast Track Applications:  For Fast Track applications, 
the NIH expedites evaluation of progress following the Phase I feasibility 
study, for transition to the Phase II funding for expanded developmental work.  
You may request Fast Track review of your application.  Information on this 
option is available at http://grants.nih.gov/grants/funding/sbirsttr1/index.pdf.

SENDING AN APPLICATION TO THE NIH:  Submit a signed, typewritten original of the 
application, including the checklist, and five signed photocopies in one package 
to: 

Center for Scientific Review
National Institutes of Health 
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710 
Bethesda, MD  20817 (for express/courier service)

APPLICATION PROCESSING:  Applications must be received by or mailed on or before 
the receipt dates noted above.  The CSR will not accept any application in 
response to this PA that is essentially the same as one currently pending 
initial review unless the applicant withdraws the pending application.  The CSR 
will not accept any application that is essentially the same as one already 
reviewed.  This does not preclude the submission of a substantial revision of an 
application already reviewed, but such application must include an Introduction 
addressing the previous critique.

PEER REVIEW PROCESS

Applications submitted for this PA will be assigned on the basis of established 
PHS referral guidelines.  An appropriate scientific review group convened in 
accordance with the standard NIH peer review procedures 
(http://www.csr.nih.gov/refrev.htm) will evaluate applications for scientific 
and technical merit.  

As part of the initial merit review, all applications will:

o  Receive a written critique 
o  Undergo a process in which only those applications deemed to have the highest 
scientific merit, generally the top half of applications under review, will be 
discussed and assigned a priority score
o  Receive a second level review by the appropriate national advisory council or 
board

REVIEW CRITERIA

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  In the 
written comments, reviewers will be asked to discuss the following aspects of 
your application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals:

o  Significance
o  Approach
o  Milestones and Proof of Principle
o  Innovation
o  Investigator
o  Environment

The scientific review group will address and consider each of these criteria in 
assigning your application's overall score, weighting them as appropriate for 
each application.  Your application does not need to be strong in all categories 
to be judged likely to have major scientific impact and thus deserve a high 
priority score.  For example, you may propose to carry out important work that 
by its nature is not innovative but is essential to move a field forward.

(1)  SIGNIFICANCE:  Does your study address an important problem?  Does the 
proposed project have commercial potential to lead to a marketable product or 
process?  What may be the anticipated commercial and societal benefits of the 
proposed activity?  If the aims of your application are achieved, how do they 
advance scientific knowledge?  Does the proposal lead to technologies (e.g., 
instrumentation, software) that will enable further discoveries?  Will the 
technology have a competitive advantage over existing/alternate technologies 
that can meet market needs? 

(2)  APPROACH:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well integrated, and appropriate to the aims of the 
project?  Do you acknowledge potential problem areas and consider alternative 
tactics?  What is the time frame for developing the proposed technologies, and 
is this time frame suitable for meeting the community's needs?  How easy will it 
be to use the proposed technology?  Are your plans adequate for the proposed 
technology, its integration as an effective solution for implementation, and 
dissemination?  If you are proposing industrial partnerships, how will they 
facilitate the development and integration of system components? 

(3)  MILESTONES (for Phase I R41 or R43 or Fast Track applications) AND PROOF OF 
PRINCIPLE (for Phase II applications):  If you are submitting a Phase I 
application, how appropriate are your proposed milestones for evaluating 
demonstration of feasibility for transition to the R42 or R44 Phase II 
development work?  Do the milestones provide an objective target for evaluating 
results?  If you are submitting a Phase II application, how well has the 
feasibility or proof of principle been demonstrated? 

(4)  INNOVATION:  Does your project employ novel concepts, approaches, or 
methods?  Are the aims original and innovative? Does your project challenge 
existing paradigms or develop new methodologies or technologies?  What is the 
throughput and cost-effectiveness of your proposed technology?  What additional 
uses can be projected for your proposed technology?

(5)  INVESTIGATOR:  Are you appropriately trained and well suited to direct this 
work?  Is the work proposed appropriate to your experience level as the 
principal investigator and to that of other researchers (if any)?

(6)  ENVIRONMENT:  Is there sufficient access to resources (e.g., equipment, 
facilities)?  Does the technical and scientific environment in which your work 
will be done contribute to the probability of success?  Does the proposed work 
take advantage of unique features of the technical and scientific environment or 
employ useful collaborative arrangements?

ADDITIONAL REVIEW CRITERIA:  In addition to the above criteria, your application 
will also be reviewed with respect to the following:

PROTECTIONS:  The adequacy of the proposed protection for humans, animals, or 
the environment, to the extent they may be adversely affected by the project 
proposed in the application. 

INCLUSION:  The adequacy of plans to include subjects from both genders, all 
racial and ethnic groups (and subgroups), and children as appropriate for the 
scientific goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated.

BUDGET:  The reasonableness of the proposed budget and the requested period of 
support in relation to the proposed research.

AWARD CRITERIA

Applications submitted in response to this PA will compete for available funds 
with all other recommended SBIR and STTR applications.  The following will be 
considered in making funding decisions for Phase I or Phase II applications:

o  Quality of the proposed project as determined by peer review
o  Availability of funds
o  Relevance to program priorities

Phase II applications will be selected for funding based on the following:

o  Quality of the proposed project as determined by peer review
o  Assessment of Phase I progress 
o  Determination that the Phase I goals were achieved
o  The project's potential for commercial success 
o  Availability of funds

Fast Track Phase II applications may be funded following submission of:

o  The Phase I progress report 
o  Other documents necessary for continuation  

REQUIRED FEDERAL CITATIONS

It is not anticipated that proposals submitted in response to this PA will 
involve human subject studies.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT:  The 
Office of Management and Budget (OMB) Circular A-110 has been revised to provide 
public access to research data through the Freedom of Information Act(FOIA) 
under some circumstances.  Data collected under SBIR and STTR grants are 
exempted.  See: http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm).

Applicants may wish to place data collected under this PA in a public archive, 
which can provide protections for the data and manage the distribution for an 
indefinite period of time.  If so, the application should include a description 
of the archiving plan in the study design and include information about this in 
the budget justification section of the application.  In addition, applicants 
should think about how to structure informed consent statements and other human 
subjects procedures given the potential for wider use of data collected under 
this award.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES:  All applications and proposals 
for NIH funding must be self-contained within specified page limitations.  
Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) 
should not be used to provide information necessary to the review because 
reviewers are under no obligation to view the Internet sites.  Furthermore, we 
caution reviewers that their anonymity may be compromised when they directly 
access an Internet site.

HEALTHY PEOPLE 2010:  The Public Health Service (PHS) is committed to achieving 
the health promotion and disease prevention objectives of "Healthy People 2010," 
a PHS-led national activity for setting priority areas. This PA is related to 
one or more of the priority areas.  Potential applicants may obtain a copy of 
"Healthy People 2010" at http://www.health.gov/healthypeople.

AUTHORITY AND REGULATIONS:  This program is described in the Catalog of Federal 
Domestic Assistance No. 93.113, 93,173, 93.242, 93.279, 93.371, 93.396, 93.821, 
93.837, 93.846, 93.847, 93.853, 93.859, 93.866 and is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health Systems 
Agency review.  Awards are made under authorization of Sections 301 and 405 of 
the Public Health Service Act as amended (15 USC 638 and 42 USC 241 and 284) and 
administered under NIH grants policies described at 
http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 42 
CFR 52 and 45 CFR Parts 74.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and discourage the use of all tobacco products.  In addition, Public 
Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain 
facilities (or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care, or early childhood 
development services are provided to children.  This is consistent with the PHS 
mission to protect and advance the physical and mental health of the American 
people.


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